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Role of Myotonic Dystrophy Protein Kinase [DMPK] in Glucose Homeostasis and Muscle Insulin Action Llagostera Martín, Esther Catalucci, Daniele Martí, Luc Liesa Torre-Marín, Montserrat Camps Camprubí, Marta Ciaraldi, Theodore P. Kondo, Richard Reddy, Sita Dillmann, Wolfgang H. Palacín Prieto, Manuel Zorzano Olarte, Antonio Ruiz-Lozano, Pilar Gomis, Ramon, 1946- Kaliman, Perla Fisiologia patològica Proteïnes quinases Malalties de l'aparell locomotor Insulina Pathological physiology Protein kinases Enfermedades del aparato locomotor Insulin Myotonic dystrophy 1 (DM1) is caused by a CTG expansion in the 3′-unstranslated region of the DMPK gene, which encodes a serine/threonine protein kinase. One of the common clinical features of DM1 patients is insulin resistance, which has been associated with a pathogenic effect of the repeat expansions. Here we show that DMPK itself is a positive modulator of insulin action. DMPK-deficient (dmpk−/−) mice exhibit impaired insulin signaling in muscle tissues but not in adipocytes and liver, tissues in which DMPK is not expressed. Dmpk−/− mice display metabolic derangements such as abnormal glucose tolerance, reduced glucose uptake and impaired insulin-dependent GLUT4 trafficking in muscle. Using DMPK mutants, we show that DMPK is required for a correct intracellular trafficking of insulin and IGF-1 receptors, providing a mechanism to explain the molecular and metabolic phenotype of dmpk−/− mice. Taken together, these findings indicate that reduced DMPK expression may directly influence the onset of insulin-resistance in DM1 patients and point to dmpk as a new candidate gene for susceptibility to type 2-diabetes. 2013-05-10T12:21:03Z 2013-05-10T12:21:03Z 2007-10 2013-05-10T12:21:03Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 1932-6203 https://hdl.handle.net/2445/43315 567842 17987120 eng Reproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0001134 PLoS One, 2007, num. 11, p. e1134 http://dx.doi.org/10.1371/journal.pone.0001134 cc-by (c) Llagostera Martín, Esther et al., 2007 http://creativecommons.org/licenses/by/3.0/es info:eu-repo/semantics/openAccess 11 p. application/pdf application/pdf Public Library of Science (PLoS) Articles publicats en revistes (Bioquímica i Biomedicina Molecular)